Age and amyloid effects on human central nervous system amyloid-beta kinetics.
Ann Neurol
; 78(3): 439-53, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-26040676
ABSTRACT
OBJECTIVE:
Age is the single greatest risk factor for Alzheimer's disease (AD), with the incidence doubling every 5 years after age 65. However, our understanding of the mechanistic relationship between increasing age and the risk for AD is currently limited. We therefore sought to determine the relationship between age, amyloidosis, and amyloid-beta (Aß) kinetics in the central nervous system (CNS) of humans.METHODS:
Aß kinetics were analyzed in 112 participants and compared to the ages of participants and the amount of amyloid deposition.RESULTS:
We found a highly significant correlation between increasing age and slowed Aß turnover rates (2.5-fold longer half-life over five decades of age). In addition, we found independent effects on Aß42 kinetics specifically in participants with amyloid deposition. Amyloidosis was associated with a higher (>50%) irreversible loss of soluble Aß42 and a 10-fold higher Aß42 reversible exchange rate.INTERPRETATION:
These findings reveal a mechanistic link between human aging and the risk of amyloidosis, which may be owing to a dramatic slowing of Aß turnover, increasing the likelihood of protein misfolding that leads to deposition. Alterations in Aß kinetics associated with aging and amyloidosis suggest opportunities for diagnostic and therapeutic strategies. More generally, this study provides an example of how changes in protein turnover kinetics can be used to detect physiological and pathophysiological changes and may be applicable to other proteinopathies.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Envelhecimento
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Sistema Nervoso Central
/
Peptídeos beta-Amiloides
/
Amiloidose
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Macau